Background: Mild traumatic brain injury (mTBI) is common among military service members returning from OEF/OIF deployments. While a history of military mTBI has been demonstrated to be associated with increased risk of negative psychological outcomes (e.g., PTSD, depression, alcohol dependence), as well as disrupted brain connectivity, it is unknown how these conditions relate to neurodegenerative conditions, such as chronic traumatic encephalopathy (CTE). Therefore, it would be of high clinical utility to identify markers, especially in vivo biological markers, that are present early in the neurodegenerative course, reliably predict further decline, and can be distinguished from confounding factors. Objective/Hypothesis: The overall goal of the proposed research is to better understand biological and psychological factors contributing to progressive functional deterioration among veterans with a history of military concussion. In particular, the methods described are intended to identify veterans demonstrating evidence of worsening cognitive disruption and/or neural degeneration. Improved characterization of long-term, ongoing damage associated with mTBI among active duty service members and veterans may improve the diagnostic and monitoring procedures used in these populations, reduce clinical costs, and improve long-term veteran health outcomes. Specific Aims: The proposed research will address two critical elements: Aim 1: Test several psychological and biological measures for utility as markers of mTBI-related neurodegeneration. (Specific Aims 1-4) Aim 2: Characterize the utility and limitations of self-report measures in the context of mTBI and comorbid psychopathology. (Specific Aims 5-6) Study Design: Participants will be 180 of the 276 OEF/OIF military service members who provided a blood sample as well as complete clinical, cognitive, self-report, and neuroimaging data during participation in one of two prior studies. All participants completed combat deployments as part of OEF or OIF, and the majority endorsed a history of mTBI and/or PTSD. Longitudinal data will be collected on the measures acquired in the prior (i.e., baseline) studies, including clinical interviews of psychopathology (SCID, CAPS) and mTBI, self- report measures of psychopathology (BDI, PCL-M) and personality (MPQ, MMPI-2), neuroimaging (MRI, EEG), and blood-based protein expression. Additional data from these instruments will be collected to specifically inform characterization of reliability. Impact: Given the high rates of mTBI during OEF/OIF deployments, along with high rates of civilian mTBI (e.g., contact sports, high risk recreational activities) among members of the military, better understanding of the long-term effects of mTBI, especially progressive neurodegenerative effects, would be of utility to the identification of soldiers at increased risk, diagnosis and intervention in early stages, and ultimately prevention efforts. The results of the proposed research may have implications for the assessment and documentation of mTBI during deployment, education of soldiers and military medical providers, long-term monitoring of service members who sustain mTBI, and enable more efficient provision of long-term care. Therefore, there are clear potential benefits for active duty military as well as for veteran care.